Challenges in lung cancer therapy during the COVID-19 pandemic

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Challenges in lung cancer therapy during the COVID-19

pandemic

Luana Calabrò, Solange Peters, Jean-Charles Soria, Anna Maria Di Giacomo,

Fabrice Barlesi, Alessia Covre, Maresa Altomonte, Virginia Vegni, Cesare

Gridelli, Martin Reck, et al.

To cite this version:

Luana Calabrò, Solange Peters, Jean-Charles Soria, Anna Maria Di Giacomo, Fabrice Barlesi, et al..

Challenges in lung cancer therapy during the COVID-19 pandemic. The Lancet Respiratory Medicine,

Elsevier, 2020, �10.1016/S2213-2600(20)30170-3�. �inserm-02546052�

Comment

www.thelancet.com/respiratory Published online April 9, 2020 https://doi.org/10.1016/S2213-2600(20)30170-3 1

Lancet Respir Med 2020

Published Online

April 9, 2020 https://doi.org/10.1016/ S2213-2600(20)30170-3

Challenges in lung cancer therapy during the COVID-19

pandemic

Coronavirus disease 2019 (COVID-19), caused by the

newly identified strain of the coronavirus family severe

acute respiratory syndrome coronavirus 2 (SARS-CoV-2),

has rapidly evolved into a worldwide pandemic and

caused a public health emergency of major international

concern.

_{As a result, a profound reorganisation of}

hospital wards and clinical activities is happening

worldwide to deal with the increasing number of

COVID-19-positive patients who require hospitalisation

and intensive care support.

_{This comprehensive}

reallocation of health resources is of particular concern

in patients such as those with underlying chronic

diseases, including cancer.

The prioritisation of health support towards patients

with COVID-19 is raising apprehension within the

medical oncology community, in which physicians

are increasingly being forced to select which patients

should receive anticancer therapy on the basis of

who is most likely to have a positive outcome.

_In

this context, the threat of COVID-19 infection might

also factor into decision making—a role which could

possibly be lessened by knowledge of the COVID-19

status of patients suitable for anticancer therapy.

_This

already dismal scenario seems to be even more severe

for patients with lung cancer because of the high risk of

interference of COVID-19 with their effective diagnostic

and therapeutic management by treating physicians.

Clinical manifestations of COVID-19 range from

asymptomatic, to mild symptoms (such as cold, fever,

cough, or other non-specific signs), to severe pneumonia

leading to acute respiratory distress syndrome, which

occurs in 17–29% of infected individuals.

_Mortality

due to COVID-19 has been reported in about 3% of

COVID-19-positive patients in the Chinese population,

while higher mortality rates are being reported in Italy,

which is, after the USA, currently the country with the

second highest number of confirmed COVID-19 cases

worldwide.

In the early phase of COVID-19-induced pneumonia,

the main CT findings include multifocal peripheral and

basal ground-glass opacities, crazy paving patterns,

traction bronchiectasis, and air bronchogram signs.

A progressive transition to consolidation, together

with pleural effusion, extensive small lung nodules,

irregular interlobular or septal thickening, and

adenopathies, characterise the more advanced phase

of the disease.

_{These radiological manifestations}

can overlap with CT findings that are often found in

patients with lung cancer upon disease progression

or onset of concomitant pneumonia due to

over-lapping opportunistic infections. Regarding clinical

manifestations, the worsening of pulmonary symptoms

during lung cancer progression can be similar to that

typical of COVID-19, adding further complexity to

the thorough assessment of the course of disease in

lung cancer patients. Together, these similarities can

pose a major challenge to clinicians in distinguishing

lung cancer evolution from a potential COVID-19

super-infection on the basis of radiological and clinical

evidence, and, importantly, these specific conditions

require very different therapeutic approaches.

Adding further complexity to this scenario,

pneumonitis can also be induced by immune checkpoint

inhibitor therapy, an effective and widely used

standard-of-care treatment for lung cancer in various treatment

lines and settings.

_{Immune checkpoint}

inhibitor-related pneumonitis has been reported in about 2% of

cancer patients,

_{with a seemingly higher incidence}

in patients with lung cancer.

_{Similar to COVID-19}

infection, the clinical symptoms of immune checkpoint

inhibitor-induced pneumonitis are often not specific,

consisting mainly of cough (or its worsening), chest

A

B

Figure: CT scans of pneumonia due to COVID-19 and immune checkpoint

inhibitor therapy

(A) Axial lung image (without intravenous contrast) of 49-year-old man with COVID-19, showing two sub-solid areas in the upper right lobe (arrows). (B) Axial lung image (without intravenous contrast) of an immune checkpoint inhibitor-treated 76-year-old man with metastatic melanoma, showing a sub-solid area and ground-glass opacities with a rounded morphology in the upper right lobe (arrows). COVID-19=coronavirus disease 2019.

Comment

2 www.thelancet.com/respiratory Published online April 9, 2020 https://doi.org/10.1016/S2213-2600(20)30170-3

pain, dyspnoea, and fever. Additionally, CT assessment

of immune checkpoint inhibitor-related pneumonitis

shows radiological findings similar to those typical

of COVID-19-induced pneumonia (figure), thus

hindering discrimination between the two clinical

entities. Similarly, tyrosine kinase inhibitors can induce

radiological patterns of interstitial-like pneumonitis,

which develops in 4% of patients with epidermal

growth factor receptor-mutant lung cancer treated with

osimertinib.

In this scenario, standard chemotherapy does not

seem to represent a suitable or potentially safer

alternative to immune checkpoint inhibitor therapy —

neither for treating physicians who want to avoid the

overlapping immune checkpoint inhibitor-related and

COVID-19-related radiological and clinical changes,

or for patients who are unsuitable for immune

checkpoint inhibitor therapy. First, combinations of

chemotherapies and immunotherapies have shown

the best efficacy and represent the standard of care in a

large group of patients without oncogene-driven lung

cancer and without high PD-L1 expression in tumour

cells. Second, the development of

chemotherapy-associated pneumonitis is known to occur in up to 16%

of treated patients,

_{and cytotoxic chemotherapy has}

immunosuppressive activity.

_{Notably, administration}

of chemotherapy within the month preceding COVID-19

diagnosis has been shown to be associated with a higher

risk of severe infection-related complications.

The clinical and biological aggressiveness of lung

malignancies clearly does not allow for anticancer

therapy to be withheld or postponed. Thus, while

awaiting specific evidence-based guidelines, the

comprehensive management of patients with lung

cancer during the COVID-19 pandemic should involve

specific and careful attention to their clinical and

radiological pulmonary signs, more so than for patients

with other types of tumour. From a practical viewpoint,

it seems reasonable to suggest that patients with lung

cancer undergo systematic testing for SARS-CoV-2 at

the beginning of treatment and whenever it is deemed

necessary by the treating physician in the course of

therapy. This strategy might become more feasible

with the increasing availability and progressive use

of real-time PCR assays that can provide COVID-19

status results within an hour.

_{Furthermore, the}

availability of laboratory IgM or IgG testing to evaluate

the exposure and immunity to SARS-CoV-2 infection

will be helpful when the COVID-19 pandemic begins to

decline. Allocating resources for these methodological

approaches to patients with lung cancer should

facilitate the most appropriate clinical management by

multidisciplinary lung cancer care teams.

LC has served as consultant or advisor to Bristol-Myers Squibb and Merck Sharp and Dohme. SP has received education grants, provided consultation, attended advisory boards, or provided lectures for AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Bioinvent, Blueprint Medicines, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, and Vaccibody, from whom she has received honoraria (all fees to institution). J-CS was employee for AstraZeneca from September, 2017, to December, 2019, and has shares in Gritstone. AMDG has served as a consultant or advisor to Incyte, Pierre Fabre, GlaxoSmithKline and Bristol-Myers Squibb, Merck Sharp Dohme, and Sanofi. FB has served as a consultant, advisor, or lecturer for AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, Eli Lilly Oncology, F Hoffmann-La Roche, Novartis, Merck, Merck Sharp and Dohme, Pierre Fabre, Pfizer, and Takeda. CG has received honoraria as consultant or advisor or speaker bureau member for AstraZeneca, Bristol-Myers Squibb, F Hoffmann-La Roche, and Merck Sharp and Dohme, and has received funds (to organisation) from Merck Sharp and Dohme. MR has served as a consultant and provided lectures for Amgen, AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Merck, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Samsung. MM has served as a consultant or advisor to Roche, Bristol-Myers Squibb, Merck Sharp and Dohme, Incyte, AstraZeneca, Amgen, Pierre Fabre, Eli Lilly, GlaxoSmithKline, Sciclone, Sanofi, Alfasigma, and Merck Serono. AC, MA, and VV declare no competing interests. We thanks Nicholas Landini of the Diagnostic Radiology Department of Ca’ Foncello Regional Hospital (Treviso, Italy), for providing the CT scan images of a COVID-19-positive patient with pneumonia. NR declares no competing interests.

Luana Calabrò, Solange Peters, Jean-Charles Soria,

Anna Maria Di Giacomo, Fabrice Barlesi, Alessia Covre,

Maresa Altomonte, Virginia Vegni, Cesare Gridelli,

Martin Reck, Naiyer Rizvi, *Michele Maio

mmaiocro@gmail.com

Center for Immuno-Oncology, Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, 53100 Siena, Italy (LC, AMDG, AC, MA, MM); NIBIT Foundation Onlus, Siena, Italy (MM); Centre Hospitalier Universitaire Vaudois, Oncology Department, Lausanne University, Lausanne, Switzerland (SP); Gustave Roussy Cancer Campus, Villejuif, France (J-CS, FB); Université Paris-Saclay, Orsay, France (J-CS); Aix Marseille University, CNRS, INSERM, CRCM, Marseille, France (FB); Radiology Unit, Rugani Hospital, Siena, Italy (VV); Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy (CG); LungenClinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (MR); and Division of Hematology/Oncology, Department of Medicine, Columbia University, New York, NY, USA (NR)

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